The mechanism of T cell activation has been studied employing both cloned T cell populations and naive heterogeneous T cell populations. Comparison has been made of T cell stimulation by antibodies directed to allotypic determinants on the T cell receptor, T cell activation by specific antigen, and T cell activation by non-receptor-mediated signaling. It has been demonstrated that both cloned and naive T cells can be triggered by the monoclonal antibody F23.1, directed toward determinants on the T cell receptor. Naive Lyt2+ T cells were activated to proliferate in the presence of soluble F23.1, IL-2, and accessory cells. Under the same conditions, L3T4+ naive T cells were unresponsive. These findings thus demonstrated a difference in the activation requirements of T cell subpopulations triggered through T cell receptor determinants. Specific "targeting" of the T cell receptor to accessory cell structures by heteroaggregates of F23.1 coupled to monoclonal anti-Ia antibody were, in contrast, capable of activating both Lyt2+ and L3T4+ T cell subpopulations. The nature of activation signals provided under these diverse conditions is currently under study. The role of endogenous lymphokines in T cell activation has been demonstrated. The proliferative response of type 2 T helper clones is inhibited by antibody specific for the lymphokine IL4, which is produced by these clones. This demonstrates that IL4 acts as an autocrine growth factor for these T cells. In addition, mRNA levels corresponding to a number of activation genes are inhibited by the presence of anti-IL4 antibody during T cell activation. In contrast, the level of IL4 mRNA is actually increased in the presence of this antibody, suggesting that an endogenously produced IL4 may normally down regulate its own transcription.